VITAL Rhythm Study

October 2, 2025 updated by: Christine M. Albert, MD, MPH, Brigham and Women's Hospital

Vitamin D and Omega-3 Trial (VITAL Rhythm Study)

The VITamin D and OmegA-3 TriaL (VITAL) is an ongoing randomized clinical trial of 25,871 U.S. men and women investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk of developing cancer, heart disease, and stroke in individuals who do not have a prior history of these illnesses. The purpose of this ancillary study is to ascertain and adjudicate atrial fibrillation (AF) outcomes for the primary aim of testing whether omega-3 fatty acid and/or vitamin D supplementation influence atrial fibrillation risk in the general population. We also plan to examine how these agents might impact the development of AF subtypes (persistent versus paroxysmal), intermediate phenotypes for heart rhythm disorders (electrocardiographic parameters), as well as explore effects on arrhythmic death and whether baseline blood levels and/or race modify treatment effects.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Atrial fibrillation and sudden cardiac death assessments, as well as blood analyses, will be conducted on the entire VITAL Study population, and ECG analyses will be limited to the Clinical and Translational Science Center (CTSC) sub-cohort of 1,054 VITAL participants who live near the Boston area and agree to participate in a series of ancillary studies in addition to the main trial.

Investigators will ascertain atrial fibrillation events utilizing self-report of physician diagnoses of atrial fibrillation received on annual questionnaires from study participants supplemented by outpatient and hospital visits for AF identified through Centers for Medicare and Medicaid Services (CMS) data linkage. Investigators will also ascertain additional information regarding atrial fibrillation diagnosis from supplementary questionnaires, and seek consent to review all inpatient and outpatient hospital records pertaining to atrial fibrillation diagnosis and evaluation. Atrial fibrillation events will be confirmed by an endpoint committee composed of cardiologists, which will also make a determination on atrial fibrillation subtype and pattern. Questionnaires that inquire about recurrent atrial fibrillation events, pattern of AF, latest medical record evaluation and treatments for AF will be sent to participants with confirmed atrial fibrillation. Medical records will be requested and reviewed an endpoint committee to determine atrial fibrillation subtype and progression. An intention-to-treat analysis examining the 5-year treatment effects of omega-3 fatty acids and vitamin D on incident atrial fibrillation, as well as subtypes at the time of diagnosis will be performed to address the primary aims. We will repeat these analyses at the end of extended follow-up to assess cumulative and post-treatment effects of omega-3 fatty acids and vitamin D and AF subtypes two years after diagnosis.

Electrocardiograms will be obtained at baseline and again after two years of treatment and follow-up among a sub-cohort of 1,054 patients being enrolled in VITAL at the CTSC. Investigators will utilize these ECG data to evaluate whether treatment with omega-3 fatty acids and vitamin D3 have significant effects on ECG measures. The ECGs will also be utilized to estimate the prevalence of asymptomatic persistent atrial fibrillation in our population not detected by our atrial fibrillation surveillance methods.

Investigators will examine baseline blood samples for participants with confirmed atrial fibrillation for the purpose of exploring whether the effect of vitamin D3 or fish oil supplementation on atrial fibrillation risk varies by the baseline blood levels of these nutrients.

Investigators will also seek additional information necessary to classify deaths as sudden or arrhythmic in origin, and cardiac deaths will be reviewed by an endpoint committee of cardiologists. Once these results have been compiled investigators will explore whether omega-3 fatty acids and/or vitamin D might have an effect on sudden and/or arrhythmic cardiac death.

Study Type

Interventional

Enrollment (Actual)

25119

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

46 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

To be eligible this ancillary study participants must be enrolled in the Vitamin D and Omega-3 Trial (VITAL; National Clinical Trial (NCT) 01169259) and meet the following criteria:

Inclusion Criteria:

- physician diagnosis of atrial fibrillation after randomization

and/or

- cardiovascular death

Exclusion Criteria:

- physician diagnosis of atrial fibrillation prior to randomization

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Vitamin D + fish oil
Dietary supplement: Vitamin D3
Vitamin D3 (cholecalciferol), 2000 IU per day.
Other Names:
  • cholecalciferol
Drug: Omega-3 fatty acids (fish oil)
Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
Active Comparator: Vitamin D + fish oil placebo
Dietary supplement: Fish oil placebo
Fish oil placebo
Dietary supplement: Vitamin D3
Vitamin D3 (cholecalciferol), 2000 IU per day.
Other Names:
  • cholecalciferol
Active Comparator: Vitamin D placebo + fish oil
Dietary supplement: Vitamin D3 placebo
Vitamin D3 placebo
Drug: Omega-3 fatty acids (fish oil)
Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
Placebo Comparator: Vitamin D placebo + fish oil placebo
Dietary supplement: Fish oil placebo
Fish oil placebo
Dietary supplement: Vitamin D3 placebo
Vitamin D3 placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Atrial Fibrillation
Time Frame: 7 years
To assess whether omega-3 fatty acids (Omacor® 840 mg eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) or vitamin D3 supplementation influences risk of atrial fibrillation in a general population of men and women without prior cardiovascular disease.
7 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Atrial Fibrillation
Time Frame: 7 years
To examine the short and long-term impacts of vitamin D3 and EPA+DHA supplementation on the development of AF subtypes.
7 years
Arrhythmic endpoints
Time Frame: 5 years
To examine the effect of vitamin D3 or EPA+DHA supplementation on electrocardiographic parameters to further understand mechanisms underlying associations with arrhythmic endpoints.
5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sudden Cardiac Death
Time Frame: 5 years
To explore effects of arrhythmic death and whether baseline blood levels and/or race modify treatment effects.
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
Cedars-Sinai Medical Center

Investigators

  • Principal Investigator: Christine M. Albert, M.D., M.P.H., Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2012

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

October 1, 2026

Study Registration Dates

First Submitted

June 25, 2014

First Submitted That Met QC Criteria

June 26, 2014

First Posted (Estimated)

June 30, 2014

Study Record Updates

Last Update Posted (Estimated)

October 7, 2025

Last Update Submitted That Met QC Criteria

October 2, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2012P002146
  • R01HL116690 (U.S. NIH Grant/Contract)

Drug and device information, study documents

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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